Publication Date

2011-05-05

Availability

Embargoed

Embargo Period

2012-10-26

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biomedical Engineering (Engineering)

Date of Defense

2011-03-17

First Committee Member

Vittorio Porciatti

Second Committee Member

Fabrice Manns

Third Committee Member

Jorge E. Bohórquez

Fourth Committee Member

Douglas R. Anderson

Fifth Committee Member

Jean-Marie Parel

Abstract

The murine eye naturally undergoes post-natal changes in eye size. This dissertation quantifies longitudinal structural and functional changes in control mice (C57BL/6J (B6), D2-Gpnmb+/SjJ) and in DBA/2J (D2) mice, which spontaneously develop elevated intraocular pressure (IOP). IOP elevation results in abnormal eye elongation, retinal nerve fiber layer (RNFL) thickness thinning and retinal ganglion cell (RGC) dysfunction and demise resembling human glaucoma. I measured structural changes with Optical Coherence Tomography (OCT), and RGC function with Pattern Electroretinogram (PERG). I also developed and refined provocation approaches (IOP elevation with changes in body posture; metabolic load with flickering light) to probe susceptibility of RGC function in D2 mice prone to glaucoma. Finally, I developed a novel system for recording, simultaneously but independently, the PERG from both eyes using asynchronous visual stimuli and deconvolution analysis. Simultaneous PERG recording from each eye was hitherto impossible due to the interocular cross-talk of the PERG signal. Altogether, the combination of these measures (OCT, PERG) and provocative conditions may represent powerful tools for glaucoma research using mouse models.

Keywords

glaucoma; intraocular pressure; retinal ganglion cell; Pattern Electroretinogram; Optical Coherence Tomography; DBA/2J (D2) mice

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